Manufacture of condensation products from trimethyl-hydroquinone



Patented Jan. 20, 1942 1 MANUFACTURE OF CONDENSATION PROD- UCTS FROM TRIIWETHYL-HYDROQUI- NONE Otto Isler, Basel, Switzerland, assignor to 1101iman-La Roche Inc., Nutley, N. J a corporation of New Jersey No Drawing. Application March 10, 1939, Serial No. 261,158. In Switzerland March 18, 1938 1 Claim. (Cl. 260-333) It has been found that trimethyl-hydroquinone-monoalkylene ethers can be obtained by causing trimethyl-hydroquinone (cumo-hydroquinone) to act on halogeno-alkylenes in the presence of agents capable of combining with acids. These trime-thyl-hydroquinone-monoa1- kylene ethers are rearranged by heating, the transformation products being converted into 2-alkyl-5-oxy-coumaranes or 2-alkyl-6-oxychromanes on treatment with acid condensation agents. In the following formulae, R and R represent hydrogen or alkyl. If both R and. R represent alkyl groups, then 2-a1kyl-6-oxychromanes are formed. If both R and R represent hydrogen, 2-a1ky1-5-oxycoumarane are obtained.

CH3 H:

CH monophytyl ether are heated in parts by CH H weight of tetraline under reflux and treated with 3 3 thl hl lkl th 1h dr 2 parts by Weight of anhydrous zinc chloride trim Yene Y mumwe' while stirring The product is allowed to coolh dr monoalkylene ether y oqumone water and petroleum ether added, the petroleum ether layer washed and dried. The condensation heating CH:

OH --oHz R CH l t 3 7 CH H-CHR OH GHzCH=O-R O 1 H: CH OH 2-elkyl-5-oxycoumarane CH; X

OH om R transiogmattion CH pro no Z-alkyl-fi-oxychromane The condensation products from trimethylhydroquinone are to be used for the manufacture of medicinal preparations and as medicinal preparations.

Example 1 2.1 parts by weight of phytyl bromide, 1.0 part by weight of trimethyl-hydroquinone and 0.9 part by weight of anhydrous potassium carbonate are heated together for hours with 15 parts by volume of acetone in an atmosphere of nitrogen under reflux. After filtering off from insoluble salts, the residue is washed several times with acetone and the acetone solution concentrated.

The residue is taken up in petroleum ether, the trimethyl-hydroquinone, which is difficultly soluble therein. filtered off and the easily soluble phytyl ether adsorbed on an aluminium oxide column. Unetherified phytyl compounds are washed through the column with 1500 parts by volume of petroleum ether. The monoether is now eluted with a mixture of per cent of methyl alcohol and 30 per cent of ether, the solvent evaporated, the residue taken up in petroleum ether and the solution first washed with aqueous methyl-alcoholic potassium hydroxide, then with dilute acid, and finally with water. After evaporation of the petroleum ether the trimethyl-hydroquinone-monophyty1 ether remains as a reddish-yellow, slightly viscous oil which forms a sublimate of trimethyl-hydroquinone on thermal decomposition.

4 parts by weight of trimethyl-hydroquinoneproducts are then fractionated by chromatographic adsorption on an aluminium oxide column. The upper grey zone contains dl-oc-tocopherol which can be eluted by a mixture of Example 2 A solution of trimethyl-hydroquinone in acetone is boiled with allyl bromide under reflux in the presence of anhydrous potassium carbonate.

The resulting mono-allyl ether of trimethylhydroquinone is heated above 200 C. for some I claim:

time and then melted with pyridine hydrochlo- A process fo the p p t o of dl-wtocoride. The 2,4,6,7-tetramethyl-5-oxycoumarane pherol which comprises heating trimethyl-hydroformed is isolated by distillation with steam and quinone-monophytyl ether to efie-ct rearrangepurified by vacuum sublimation. It forms crys- 5 ment, and treating the transformation product tals melting at 124-125 C. A methyl-alcoholic with an acid condensing agent.

solution of silver nitrate is reduced by the cou-.

marane on heating. OTTO ISLER. 

